Chapter seven

MEASURES OF ASSOCIATION

Tiruneh A. (BSc, MPH)

 Measures of Association
• Summarize the frequency measures of two
variables into a single summary parameter
that estimates the degree of association.

• Requires comparing two groups:

Exposed Vs Unexposed
With outcome Vs Without Outcome
 Measures of association cont…
• the RR & OR are the 2 most frequently used
measures of association
• Epidemiologic data are often presented in the
form of a two-by-two table (four-fold or
contingency table)
• Generally we can have r-by-c table
 Presentation of data in a two-by-two table

Disease
Yes No Total
Exposure a b
Yes a+b
  No c d c+d
  Total a+c b+d a+b+c+d
 
 Presentation of data in a two-by-two table
cont…

• In cohort studies with variable lengths of

follow-up, a different type two-by-two table is
used
• The numbers of person-time units for exposed
and nonexposed subjects are provided rather
than the total numbers of individuals in each
group
 Presentation of data in a two-by-two table
cont…

Disease
Yes No Person-time units
Exposure
Yes a - PY1
No - PYo
c
a+c - PY1 + PYo
 
How strong is the association?
 1. Relative risk (Risk ratio)

• Indicate the likelihood of developing the disease in

the exposed group relative to those who are not
exposed
• For a cohort study with count data

RR = Ie = CIe =a/(a+b)
Io CIo c/(c+d)
 Example 1

Table 1: data from a cohort study of oral contraceptive (OC) use and
bacteruria among women aged 16-49 years

Bacteruria
Yes No Total

Current OC use
Yes 27 455 482
No 77 1831 1908
Total 104 2286 2390
 Example cont…
• RR = a/(a+b) =27/482 =1.4
c/(c+d) 77/1908
• Interpretation – the risk of developing bacterium in OC
users is 1.4 times that of nonusers. or
• the risk of developing bacterium in OC users is 40% higher
than nonusers (i.e 1.4 minus the null value of 1.0)
• Reverse Interpretation – the risk of developing bacterium
in OC nonusers is 0.71 that of OC users (1/1.4 =0.71). or
• the risk of developing bacterium in OC nonusers is 30%
less than OC users (i.e 0.71 minus the null value of 1.0)
 Example cont…
Table 2: Data from a cohort study of postmenopausal hormone
use and coronary heart disease among female nurses

Coronary heart disease

Yes No Person-years

Postmenopausal
hormone use
Yes 30 - 54,308.7
No 60 - 51,477.5
Total 90 105,786.2
 Example cont…
• RR = Ie =IDe = a/PY1 = 30/54,308.7 = 0.5
Io IDo c/PYo 60/51,477.5

• Interpretation:  women who used

postmenopausal hormones had 0.5 times, or
only half, the risk of developing coronary
heart disease compared with nonusers.
 Example cont…
• RR= 1 indicates no association
• RR > 1 indicates a positive association, or an
increased risk among those exposed to a factor.
• RR < 1 indicates negative association, which means
the exposure is preventive
• In general the strength of association can be
considered:
High - if the RR is 3.0 or more
Moderate – if the RR is from 1.5 to 2.9
Weak – if the RR is from 1.2 to 1.4
 2) Odds ratio
• In case control and cross sectional studies RR can be
estimated by calculating the ratio of the odds of exposure
among the cases to that among the controls
• odds – the ratio of the probability of occurrence of an
event to that of nonoccurrence
• OR indicates the likelihood of having been exposed
among cases relative to controls
Odds ratio= Odds of disease among exposed group
Odds of disease among non exposed
or
Odds ratio= Odds of exposure among disease group
Odds of exposure among non diseased group
Odds ratio…
 Odds ratio…
Odds of disease among exposed group = (a/a + b) / (b/a +b )
Odds of disease among non exposed = c/c + d / (d/c +d )
Odds of exposure among disease group = a/a + c / (c/a +c )
Odds of exposure among non diseased group = b/b + d / (d/b + d )
 OR= ((a/a + b) / (b/a +b )) / ((c/c + d)/ (d/c + d))
After simplification, OR = ad / bc
Similarly:

 OR= ((a/a + c) / (c/a + c )) / ((b/b + d)/ (d/b + d))

After simplification, OR = ad / bc
 Odds Ratio

 Thus ad/bc represents odds ratio (relative odds) in both cohort

and case-control studies
 Odds Ratio (OR) is a good estimate of the relative risk when the
disease is rare

 If OR = 1 No association between disease and exposure

 If OR > 1 Positive association between disease and exposure

 If OR < 1 Negative association between disease and exposure

(Exposure may be protective of the disease)
 Confidence interval for OR
 Used to test the presences of statistically significant association

 To construct Confidence interval for OR, first construct

Confidence interval for regression coefficient (ln OR =
logarithms of OR = denoted by B )
 S.E of ( ln OR) = (1/a+1/b+1/c+1/d)½

 95% CI for B =ln OR±1.96*S.E of ( ln OR)]

= ln OR±1.96*(1/a+1/b+1/c+1/d)½
Where,
S.E = standard error
 Confidence interval for OR

 95% CI for OR =e [ln OR±1.96*S.E of ( ln OR)]

½]
=e[ ln OR±1.96*(1/a+1/b+1/c+1/d)

 95% CI for OR =e LLB , eULB

 Where, LLB =lower limit of regression coefficient and

LLB =Uper limit of regression coefficient

 Example 2
A case control study was conducted on 200 cases of heart
disease and 400 controls to determine whether heart disease is
associated with smoking status. The results are shown in the
table below
CHD
Yes No Total
Smoking
Yes a=112 b=176 288
No c=88 d=224 312

Total 200 400 600

ad 112 x 224
OR    1.62
bc 176 x88
 Confidence interval for OR

 95% CI for OR =e [ln OR±1.96*S.E (ln OR)]

=e[ln OR±1.96*√ (1/a+1/b+1/c+1/d) ]
=e [ln 1.62±1.96*√ (1/112+1/176+1/88c+1/224) ]

OR = 1.62
95% CI = (1.13 , 2.31)

Interpretation: there is statistically significant association between

heart disease and smoking because the 95% CI does not contain the
null value 1.
 Example 3
Table 3: Data from a case-control study of current oral
contraceptive (OC) use and MI in pre-menopausal female nurses

Myocardial infarction
Yes No Total

Current OC use
Yes 23 304 327
No 133 2816 2949
Total 156 3120 3276
 Example cont…
• OR = ad = (23)(2816) = 1.6
bc (304)(133)
• The odds of developing MI in women who were current
OC users is 1.6 times that of nonusers
• The odds of developing MI in women who were current
OC users is 60% higher than that of nonusers
reverse interpretation
• The odds of developing MI in women who were not
current OC users is 0.63 times that of users
• The odds of developing MI in women who were current
OC users is 37% less than that of nonusers
 Example 4
Table 4: Calculation of RRs from a cohort study of postmenopausal hormone use
and CHD with several exposure categories

CHD Person-years

Postmenopausal
hormone use
Ever use 30 54,308.7
Past use 19 24,386.7
Current use 11 29,922.0
Never use 60 51,477.5
Ever Vs never use: RR= 0.5
Past Vs never use: RR=0.7
Current Vs never use: RR=0.3
 Odds Ratio as estimator of Relative Risk

OR is a valid estimator of RR if:

• Cases are incident and drawn from a known and
defined population
• Controls are drawn from the same defined
population and would have been in the case group
if they had the disease;
• Controls are selected in an unbiased way
• the disease is rare
What is the excess risk among
exposed individuals?
3) Attributable Risk (AR) or Risk Difference (RD)

• provides information about the absolute effect of the

exposure or the excess risk of disease in those exposed
compared with those nonexposed
• AR is the portion of the incidence of a disease in the exposed
that is due to the exposure.
• It is the incidence of a disease in the exposed that would be
eliminated if exposure were eliminated.
• AR = Ie - Io
• In a cohort study, AR is calculated as the difference of
cumulative incidences (risk difference) or incidence density
(rate difference) depending on the study design
 AR cont…
• For example in the study of OC use and bacteruria:
• AR=27/482 – 77/1908 = 0.01566 = 1566/105
• Thus, the excess occurrence of bacteruria among OC users
attributable to their OC use is 1566 per 100,000.

• AR is used to quantify the risk of disease in the exposed group

that can be considered attributable to the exposure by
removing the risk of disease that would have occurred
anyway due to other causes (the risk in the non-exposed).
 AR cont…
• The interpretation of the AR is dependent on the
assumption that a cause-effect relationship exists
between exposure and disease
• AR=0 - no association
• AR > 0 indicates
– the number of cases of the disease among the exposed
that can be attributable to the exposure itself, or
– alternatively, the number of cases of the disease among
the exposed that could be eliminated if the exposure were
eliminated
• Thus, the AR can be useful as a measure of the public
health impact of a particular exposure
 Presence of Association


Relative risk  1
Odds Ratio  1 1

Attributable risk 0 0
 What proportion of cases is
attributed to the actual exposure
among exposed people?
4) Attributable Risk Percent (AR%) or the Attributable-
rate percent, or Attributable Proportion, or Etiologic
fraction
• AR% estimate the proportion of the disease among
the exposed that is attributable to the exposure, or
• AR% is the percent of the incidence of a disease in
the exposed that is due to the exposure.
• It is the percent of the incidence of a disease in the
exposed that would be eliminated if exposure were
eliminated.
• the proportion of the disease in that group that
could be prevented by eliminating the exposure
 AR% cont…
AR% = AR X 100= (Ie – Io) X 100
Ie Ie

• Example: In the cohort study of OC use and bacteruria,

• AR% = 1566/105x 1OO = 27.96%
27/482
Interpretation: If OC use does cause bacteruria, about 28% of
bacteruria among women who use OCs can be attributable to
their OC use and could therefore be eliminated if they did not
use OCs
What is the excess risk among the general
population that is due to exposure of
interest?
 5. Population Attributable Rate or Risk (PAR)

• Estimates the portion of disease occurring in

the total population attributable to the
exposure factor
• PAR is the portion of the incidence of a
disease in the population (exposed and non
exposed) that is due to exposure.
• It is the incidence of a disease in the
population that would be eliminated if
exposure were eliminated
 PAR cont…
• It helps to determine which exposures have
the most relevance to the health of a
community
• PAR = IT - Io
• Alternatively PAR = (AR) (Pe)
 PAR cont…
• Example: the PAR of bacteruria associated with
OC use (Table 1) is:
PAR = IT - Io = 104/2390 – 77/1908 = 316/105/year
•  Or alternatively
PAR = (AR) (Pe) = 1566/105 X (482/2390)=
316/105/year
• Thus, if OC use were stopped, the excess annual
incidence rate of bacteruria that could be
eliminated among women in this study is 316
per 100,000.
 What proportion of cases is
attributed to the actual exposure
among the general population?
 5) Population Attributable Risk Percent (PAR%)

• expresses the proportion of disease in the study

population that is attributable to the exposure
and thus could be eliminated if the exposure
were eliminated.

• PAR% is the percent of the incidence of a disease

in the population (exposed and non exposed)
that is due to exposure.
 PAR% cont…
• It is the percent of the incidence of a disease
in the population that would be eliminated if
exposure were eliminated.

PAR% = PAR X 100

IT
 PAR% cont…
• For example: in the cohort study of OC use
and bacteruria (Table 1)
• PAR% = 316 x 100 = 7.3%
4351.5
• Thus, if OC use causes bacteruria, about 7
percent of all the bacteruria in the study
population could be prevented if OC use were
eliminated.